Background Initial orthograde root canal therapy (RCT) is used to treat dentoalveolar pathosis. The affect RCT has on pain intensity has been frequently reported, but the affect on other dimensions of pain has not. Also, the lack of large prospective studies involving diverse groups of patients and practitioners that are not involved in data collection suggest that there are multiple opportunities for bias to be introduced when this data is systematically aggregated. Method This prospective observational study assessed pain intensity, duration, and its interference with daily activities among RCT patients. Sixty-two practitioners (46 general dentists, 16 endodontists) in the National Dental Practice-Based Research Network enrolled patients requiring RCT. Patient reported data were collected before, immediately following, and one week after treatment using the Graded Chronic Pain Scale. Results Enrollment of 708 patients was completed over 6 months with 655 patients (93%) providing one-week follow-up data. Prior to treatment, patients reported a mean (±standard deviation) worst pain intensity of 5.3±3.8 (0-10 scale), 50% had “severe” pain (≥7), and mean days in pain and days pain interfered with activities were 3.6±2.7 and 0.5±1.2, respectively. Following treatment, patients reported a mean worst pain intensity of 3.0±3.2, 19% had “severe” pain, and mean days in pain and days with pain interference were 2.1±2.4 and 0.4±1.1, respectively. All changes were statistically significant (p<0.0001). Conclusions RCT is an effective treatment for patients experiencing pain, significantly reducing pain intensity, duration, and related interference. Further research is needed to reduce the proportion of patients reporting “severe” post-operative pain.